tbuckley/cabot-search huggingface dataset:
Osteosarcoma PDX-Derived Cell Line Models for Preclinical Drug Evaluation Demonstrate Metastasis Inhibition by Dinaciclib through a Genome-Targeted Approach
Authors: Courtney R. Schott, Amanda L. Koehne, Leanne C. Sayles, Elizabeth P. Young, Cuyler Luck, Katherine Yu, Alex G. Lee, Marcus R. Breese, Stanley G. Leung, Hang Xu, Avanthi Tayi Shah, Heng-Yi Liu, Aviv Spillinger, Inge H. Behroozfard, Kieren D. Marini, Phuong T. Dinh, María V. Pons Ventura, Emma N. Vanderboon, Florette K. Hazard, Soo-Jin Cho, Raffi S. Avedian, David G. Mohler, Melissa Zimel, Rosanna Wustrack, Christina Curtis, Marina Sirota, E. Alejandro Sweet-Cordero
Journal: Clinical Cancer Research (2023)

Models to study metastatic disease in rare cancers are needed to advance preclinical therapeutics and to gain insight into disease biology. Osteosarcoma is a rare cancer with a complex genomic landscape in which outcomes for patients with metastatic disease are poor. As osteosarcoma genomes are highly heterogeneous, multiple models are needed to fully elucidate key aspects of disease biology and to recapitulate clinically relevant phenotypes.
Einkorn genomics reveals ancient roots of domesticated wheat
Authors: Muhammad Arslan Mahmood, Shahid Mansoor
Journal: Cell Genomics (2023)

Wheat is an important staple food crop that underwent complex genome duplications. During domestication, genetic changes occurred, improving modern wheat, but understanding its phylogenetic history has been lacking. Mahmood and Mansoor discuss a recent publication demonstrating the evolutionary history of domesticated wheat (Triticum monococcum), providing opportunities for advancements in cereal improvement.
Molecularly targetable cell types in mouse visual cortex have distinguishable prediction error responses
Authors: Sean M. O’Toole, Hassana K. Oyibo, Georg B. Keller
Journal: Neuron (2023)

Predictive processing postulates the existence of prediction error neurons in cortex. Neurons with both negative and positive prediction error response properties have been identified in layer 2/3 of visual cortex, but whether they correspond to transcriptionally defined subpopulations is unclear. Here we used the activity-dependent, photoconvertible marker CaMPARI2 to tag neurons in layer 2/3 of mouse visual cortex during stimuli and behaviors designed to evoke prediction errors. We performed single-cell RNA-sequencing on these populations and found that previously annotated Adamts2 and Rrad layer 2/3 transcriptional cell types were enriched when photolabeling during stimuli that drive negative or positive prediction error responses, respectively. Finally, we validated these results functionally by designing artificial promoters for use in AAV vectors to express genetically encoded calcium indicators. Thus, transcriptionally distinct cell types in layer 2/3 that can be targeted using AAV vectors exhibit distinguishable negative and positive prediction error responses.
A robust deep learning workflow to predict CD8 + T-cell epitopes
Authors: Chloe H. Lee, Jaesung Huh, Paul R. Buckley, Myeongjun Jang, Mariana Pereira Pinho, Ricardo A. Fernandes, Agne Antanaviciute, Alison Simmons, Hashem Koohy
Journal: Genome Medicine (2023)

Abstract Background T-cells play a crucial role in the adaptive immune system by triggering responses against cancer cells and pathogens, while maintaining tolerance against self-antigens, which has sparked interest in the development of various T-cell-focused immunotherapies. However, the identification of antigens recognised by T-cells is low-throughput and laborious. To overcome some of these limitations, computational methods for predicting CD8 + T-cell epitopes have emerged. Despite recent developments, most immunogenicity algorithms struggle to learn features of peptide immunogenicity from small datasets, suffer from HLA bias and are unable to reliably predict pathology-specific CD8 + T-cell epitopes. Methods We developed TRAP (T-cell recognition potential of HLA-I presented peptides), a robust deep learning workflow for predicting CD8 + T-cell epitopes from MHC-I presented pathogenic and self-peptides. TRAP uses transfer learning, deep learning architecture and MHC binding information to make context-specific predictions of CD8 + T-cell epitopes. TRAP also detects low-confidence predictions for peptides that differ significantly from those in the training datasets to abstain from making incorrect predictions. To estimate the immunogenicity of pathogenic peptides with low-confidence predictions, we further developed a novel metric, RSAT (relative similarity to autoantigens and tumour-associated antigens), as a complementary to ‘dissimilarity to self’ from cancer studies. Results TRAP was used to identify epitopes from glioblastoma patients as well as SARS-CoV-2 peptides, and it outperformed other algorithms in both cancer and pathogenic settings. TRAP was especially effective at extracting immunogenicity-associated properties from restricted data of emerging pathogens and translating them onto related species, as well as minimising the loss of likely epitopes in imbalanced datasets. We also demonstrated that the novel metric termed RSAT was able to estimate immunogenic of pathogenic peptides of various lengths and species. TRAP implementation is available at: https://github.com/ChloeHJ/TRAP . Conclusions This study presents a novel computational workflow for accurately predicting CD8 + T-cell epitopes to foster a better understanding of antigen-specific T-cell response and the development of effective clinical therapeutics.
Retraction Note: HOXA7 plays a critical role in metastasis of liver cancer associated with activation of Snail
Authors: Bo Tang, Guangying Qi, Xiaoyu Sun, Fang Tang, Shengguang Yuan, Zhenran Wang, Xingsi Liang, Bo Li, Shuiping Yu, Jie Liu, Qi Huang, Yangchao Wei, Run Zhai, Biao Lei, Xinjin Guo, Songqing He
Journal: Molecular Cancer (2023)
Hydrogen Sulfide Gas Amplified ROS Cascade: FeS@GOx Hybrid Nanozyme Designed for Boosting Tumor Chemodynamic Immunotherapy (Adv. Healthcare Mater. 23/2023)
Authors: Wanying Sun, Chengyuan Zhu, Juan Song, Shi‐Chen Ji, Bang‐Ping Jiang, Hong Liang, Xing‐Can Shen
Journal: Advanced Healthcare Materials (2023)

Hybrid Nanoenzymes In article 2300385 by Xing-Can Shen and co-workers, a bioinspired metalloprotein-like hybrid nanozyme (FeS@GOx) is designed by incorporating the FeS nanozyme as brand-new cofactors within natural GOx protein scaffolds, providing a feasible H2S gas amplified ROS cascade strategy for precise and efficient tumor chemodynamic immunotherapy.
Natural Chlorogenic Acid Planted Nanohybrids with Steerable Hyperthermia for Osteosarcoma Suppression and Bone Regeneration (Adv. Healthcare Mater. 23/2023)
Authors: Yu‐ying Yang, Yuan Zheng, Jun‐jin Liu, Zhuang‐peng Chang, Yue‐hua Wang, Yun‐yun Shao, Rui‐gang Hou, Xiao Zhang
Journal: Advanced Healthcare Materials (2023)

Catechol-Based Nanomedicines In article 2300325, Yun-yun Shao, Rui-gang Hou, Xiao Zhang and co-workers, report a nanohybrid self-assembled from chlorogenic acid and gold nanorods through robust Au-catechol interface actions, featuring precise nanostructures, great water solubility, good stability and adjustable hyperthermia generating capacity. This integrated nanohybrid could not only severely trigger apoptosis and suppress tumor growth with strong hyperthermia but also promote the expression of heat shock proteins and induce prominent osteogenic differentiation with controllable mild NIR irradiation.
Copper‐Single‐Atom Coordinated Nanotherapeutics for Enhanced Sonothermal‐Parallel Catalytic Synergistic Cancer Therapy (Adv. Healthcare Mater. 23/2023)
Authors: Ye Qi, Shuangsong Ren, Junwei Ye, Shengnan Bi, Lei Shi, Yueguang Fang, Guangyao Wang, Y. Zou Finfrock, Jun Li, Ying Che, Guiling Ning
Journal: Advanced Healthcare Materials (2023)

Sonothermal Therapy In article 2300291 by Junwei Ye, Ying Che, Guiling Ning, and co-workers, a novel “B–H” interfacialconfined coordination strategy is reported to synthesize hyaluronic acid-functionalized single copper atoms dispersed over boron imidazolate framework-derived nanocubes to achieve sonothermal-catalytic synergistic therapy. This study highlights the applications of single-atomcoordinated nanotherapeutics in synergistic therapy, which may open up new opportunities in biomedical research.
Bioprinting of Cardiac Tissue in Space: Where Are We? (Adv. Healthcare Mater. 23/2023)
Authors: Kevin Tabury, Emil Rehnberg, Bjorn Baselet, Sarah Baatout, Lorenzo Moroni
Journal: Advanced Healthcare Materials (2023)

Bioprinting in Space 3D bioprinting in space is the next frontier for tissue engineering and is already being explored by several space agencies and companies. With this cover, Kevin Tabury, Lorenzo Moroni, and co-workers illustrate future hopes to print whole organs in space for applications on Earth and in space. This perspective (article 2203338) provides the current state of cardiac bioprinting in space.
Gold‐Enhanced Brachytherapy by a Nanoparticle‐Releasing Hydrogel and 3D‐Printed Subcutaneous Radioactive Implant Approach (Adv. Healthcare Mater. 23/2023)
Authors: Mariia Kiseleva, Théophraste Lescot, Svetlana V. Selivanova, Marc‐André Fortin
Journal: Advanced Healthcare Materials (2023)

Radiosensitizers In article 2300305 by Marc-André Fortin and co-workers, the development of a 3D printable gold nanoparticle (AuNP)-containing hydrogel adapted to topical brachytherapy applications is reported. Localized cervical cancer is selected as a case study. The 3D printable hydrogel formulation allows the particles to be delivered using tailored dosage forms. Once in the tumor, AuNPs generate numerous reactive oxygen species, lethal to cancer cells.
Advances in Microgravity Directed Tissue Engineering (Adv. Healthcare Mater. 23/2023)
Authors: Yi Cui, Weiyuan Liu, Shuaijing Zhao, Yannan Zhao, Jianwu Dai
Journal: Advanced Healthcare Materials (2023)

Microgravity Microgravity offers excellent advantages for tissue engineering by modulating cellular morphology, metabolism, secretion, proliferation, and stem cell differentiation. In article 2202768 by Yannan Zhao, Jianwu Dai and co-workers, current simulated-microgravity devices and cutting-edge advances of microgravity for biomaterials-dependent or biomaterials-independent tissue engineering are summarized and discussed to offer a reference for guiding further exploration of simulated microgravity strategies to produce engineered tissues.
Simplified consent in cluster randomised trials: the new EU Clinical Trials Regulation does not provide sufficient guidance
Authors: Cory E Goldstein, Rieke van der Graaf
Journal: BMJ (2023)

<b>Cory Goldstein and Rieke van der Graaf</b> argue that the new EU Clinical Trials Regulation on informed consent in cluster randomised trials is ambiguous and could lead to an overuse of opt-out consent approaches that provide inadequate protections for research participants
Global epidemiology of atopic dermatitis: a comprehensive systematic analysis and modelling study
Authors: Jingru Tian, Dingyao Zhang, Yi Yang, Yaqing Huang, Lu Wang, Xu Yao, Qianjin Lu
Journal: British Journal of Dermatology (2023)

Abstract Background Atopic dermatitis (AD) is the leading cause of the global burden from skin disease; no study has provided global and country-specific epidemiological estimates of AD. Objectives To quantify global, regional and country-specific estimates of the epidemiology of AD. Methods A comprehensive search for epidemiological studies in AD was conducted in four electronic databases (PubMed, Embase, Web of Science and China National Knowledge Infrastructure). A Bayesian hierarchical linear mixed model was constructed to calculate epidemiological estimates of AD considering the heterogeneity of regions, countries, type of diagnoses and age strata. Results In total, 344 studies met the inclusion criteria. Incidence varied substantially with the location and age of the surveyed participants. The global prevalence of AD and the population affected by AD were estimated to be 2.6% [95% uncertainty interval (UI) 1.9–3.5] and 204.05 million people, respectively. Around 101.27 million adults and 102.78 million children worldwide have AD, corresponding to prevalence rates of 2.0% (95% UI 1.4–2.6) and 4.0% (95% UI 2.8–5.3), respectively. Females were more likely to suffer from AD than males: the global prevalence of AD in females was 2.8% (95% UI 2.0–3.7%) and affected 108.29 million people, while in males the corresponding estimates were 2.4% (95% UI 1.7–3.3%) and 95.76 million people. Conclusions Epidemiological AD data are lacking in 41.5% of countries worldwide. The epidemiology of AD varies substantially with age and sex and is distributed unequally across geographical regions.
Drivers of deep molecular response and long‐term outcomes in patients with core binding factor acute myeloid leukemia
Authors: Parth C. Patel, Somedeb Ball, Akriti G. Jain, Chen Wang, Mohammad O. Hussaini, Luis E. Aguirre, Onyee Chan, Seongseok Yun, Andrew Kuykendall, Eric Padron, Kendra Sweet, Jeffrey E. Lancet, Rami S. Komrokji, David A. Sallman
Journal: American Journal of Hematology (2023)

A swimmer plot on clinical course of patients undergoing allogeneic stem cell transplant for core binding factor acute myeloid leukemia.
Transfused Red Blood Cell Characteristics and Kidney Transplant Outcomes Among Patients Receiving Early Posttransplant Transfusion
Authors: Emilie Gaiffe, Dewi Vernerey, Laurent Bardiaux, Franck Leroux, Aurelia Meurisse, Jamal Bamoulid, Cecile Courivaud, Philippe Saas, Marc Hazzan, Pierre Tiberghien, Didier Ducloux
Journal: JAMA Network Open (2023)

Importance Red blood cell transfusion (RBCT) is frequently required in the early post–kidney transplant period, but long-term outcomes associated with RBCT is controversial. Therefore, it may be relevant to investigate the association between RBCT characteristics and transplant outcomes. Objective To study the association between RBC storage duration and transplant outcomes. Design, Setting, and Participants This was a nationwide retrospective cohort study based on data linking between 2 prospective French nationwide registries. Clinical transplant parameters, outcomes, and RBCT characteristics were extracted from the CRISTAL registry of the Agence de la Biomédecine and the national database of the Etablissement Français du Sang. All 12 559 patients having received a first kidney transplant in France between January 1, 2002, and December 31, 2008, were included. Patients were followed up from transplant to graft loss, death with a functional graft, or data retrieval in June 2016. Data were analyzed from April 2019 to June 2022. Exposures Clinical outcomes of transplant recipients who underwent early RBCT were analyzed considering transfusion characteristics. Main Outcomes and Measures Cox proportional hazards regression models were fitted to evaluate transplant failure defined as graft loss or death with a functional graft. Results Among 12 559 patients who underwent kidney transplant, 3483 received an RBCT during the first 14 days posttransplant. The median (IQR) age of patients was 53.0 (41.5-61.2) years, and 1929 patients (55.4%) were male. Median (IQR) follow-up was 7.8 (7.6-8.0) years. In multivariable analysis, longer (vs shorter) storage duration of transfused RBC was associated with a decrease in risk of transplant failure (hazard ratio, 0.99; 95% CI, 0.98-1.00 for each additional storage day; P = .06). Patients transfused with at least 1 RBC unit stored for more than 20 days had a 5% absolute decrease in transplant failure at 3 years and 7% at 5 years compared with those who received RBC stored for less than 20 days. Conclusions and Relevance In this study, longer RBC storage duration was associated with a decreased risk of transplant failure among patients who received kidney transplants and RBC transfusions. Preferential use of RBC with longer storage duration might improve kidney graft survival following transplant and transfusion.
Global VALIANT study: ‘lifting the lid’ on disappointment and frustration with the lack of effective treatment for vitiligo
Authors: Alia Ahmed, Viktoria Eleftheriadou
Journal: British Journal of Dermatology (2023)

Journal Article Corrected proof Global VALIANT study: ‘lifting the lid’ on disappointment and frustration with the lack of effective treatment for vitiligo Get access Alia Ahmed, Alia Ahmed Writing - original draft, Writing - review & editing Frimley Health NHS Foundation Trust, FrimleyBarts Health NHS Trust, London Correspondence: Alia Ahmed. Email: dr.alia.ahmed@nhs.net Search for other works by this author on: Oxford Academic Google Scholar Viktoria Eleftheriadou Viktoria Eleftheriadou Writing - original draft, Writing - review & editing Department of Dermatology, The Royal Wolverhampton NHS Trust, Wolverhampton, UK Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad336, https://doi.org/10.1093/bjd/ljad336 Published: 14 September 2023 Article history Received: 23 August 2023 Revision received: 03 September 2023 Accepted: 06 September 2023 Published: 14 September 2023 Corrected and typeset: 17 October 2023
Metabolic targeting of platelets to combat thrombosis: dawn of a new paradigm?
Authors: Gagan D Flora, Manasa K Nayak, Madankumar Ghatge, Anil K Chauhan
Journal: Cardiovascular Research (2023)

Abstract Current antithrombotic therapies used in clinical settings target either the coagulation pathways or platelet activation receptors (P2Y12 or GPIIb/IIIa), as well as the cyclooxygenase (COX) enzyme through aspirin. However, they are associated with bleeding risk and are not suitable for long-term use. Thus, novel strategies which provide broad protection against platelet activation with minimal bleeding risks are required. Regardless of the nature of agonist stimulation, platelet activation is an energy-intensive and ATP-driven process characterized by metabolic switching toward a high rate of aerobic glycolysis, relative to oxidative phosphorylation (OXPHOS). Consequently, there has been considerable interest in recent years in investigating whether targeting metabolic pathways in platelets, especially aerobic glycolysis and OXPHOS, can modulate their activation, thereby preventing thrombosis. This review briefly discusses the choices of metabolic substrates available to platelets that drive their metabolic flexibility. We have comprehensively elucidated the relevance of aerobic glycolysis in facilitating platelet activation and the underlying molecular mechanisms that trigger this switch from OXPHOS. We have provided a detailed account of the antiplatelet effects of targeting vital metabolic checkpoints such as pyruvate dehydrogenase kinases (PDKs) and pyruvate kinase M2 (PKM2) that preferentially drive the pyruvate flux to aerobic glycolysis. Furthermore, we discuss the role of fatty acids and glutamine oxidation in mitochondria and their subsequent role in driving OXPHOS and platelet activation. While the approach of targeting metabolic regulatory mechanisms in platelets to prevent their activation is still in a nascent stage, accumulating evidence highlights its beneficial effects as a potentially novel antithrombotic strategy.
Geographical Variation in Social Determinants of Female Breast Cancer Mortality Across US Counties
Authors: Taylor Anderson, Dan Herrera, Franchesca Mireku, Kai Barner, Abigail Kokkinakis, Ha Dao, Amanda Webber, Alexandra Diaz Merida, Travis Gallo, Mariaelena Pierobon
Journal: JAMA Network Open (2023)

Breast cancer mortality is complex and traditional approaches that seek to identify determinants of mortality assume that their effects on mortality are stationary across geographic space and scales.
Intra- vs. Interhost Evolution of SARS-CoV-2 Driven by Uncorrelated Selection—The Evolution Thwarted
Authors: Mei Hou, Jingrong Shi, Zanke Gong, Haijun Wen, Yun Lan, Xizi Deng, Qinghong Fan, Jiaojiao Li, Mengling Jiang, Xiaoping Tang, Chung-I Wu, Feng Li, Yongsen Ruan
Journal: Molecular Biology and Evolution (2023)

Abstract In viral evolution, a new mutation has to proliferate within the host (Stage I) in order to be transmitted and then compete in the host population (Stage II). We now analyze the intrahost single nucleotide variants (iSNVs) in a set of 79 SARS-CoV-2 infected patients with most transmissions tracked. Here, every mutation has two measures: 1) iSNV frequency within each individual host in Stage I; 2) occurrence among individuals ranging from 1 (private), 2–78 (public), to 79 (global) occurrences in Stage II. In Stage I, a small fraction of nonsynonymous iSNVs are sufficiently advantageous to rise to a high frequency, often 100%. However, such iSNVs usually fail to become public mutations. Thus, the selective forces in the two stages of evolution are uncorrelated and, possibly, antagonistic. For that reason, successful mutants, including many variants of concern, have to avoid being eliminated in Stage I when they first emerge. As a result, they may not have the transmission advantage to outcompete the dominant strains and, hence, are rare in the host population. Few of them could manage to slowly accumulate advantageous mutations to compete in Stage II. When they do, they would appear suddenly as in each of the six successive waves of SARS-CoV-2 strains. In conclusion, Stage I evolution, the gate-keeper, may contravene the long-term viral evolution and should be heeded in viral studies.